Building a molecular lasso

Chemists at KACST are working to build molecules that may perform useful tasks as tiny molecular switches, springs or transporters. Teaming up with a Nobel Prize winning chemist in the US, they have helped create a molecular ‘lasso’ that can be induced to shift reversibly between two very different structural states. 

Majed Nassar and Youssry Botros of KACST’s Joint Center of Excellence in Integrated Nano-Systems, collaborated with researchers led by Fraser Stoddart at Northwestern University in Illinois. Stoddart is renowned for building molecules that could form components such as wheels, gears and levers for use in nanoscale machinery. 

The world already contains many molecules that move natural materials and assemble and degrade them as required. The researchers took inspiration from natural molecules called ‘lasso peptides’.  They aimed to create a similar synthetic and stable molecular loop attached to a longer ‘rope’ section, with the rope able to switch between the free state and the state in which it is threaded through the loop of the lasso. 

They built the loop from six linked rings, each containing six bonded carbon atoms. The long rope-like region has a chain of carbon atoms linked with other atomic rings. A key challenge for the researchers was to find a way to induce the molecule to change reversibly between its free and threaded states. By adjusting the chemical structure, they were able to get specific chemical or electrochemical stimuli to trigger that change. In exploring the options, they gained useful insights into how small structural changes can lead to significantly different properties. 

The researchers point out that their creation has potential as a molecular actuator: a component that can be induced to move in a specific way by some appropriate stimulus. Some possible applications might use the molecules as springs, allowing synthetic materials to shrink and expand on demand. More adventurously, the end of the rope region might be engineered to bind to some other molecule and move it across cell membranes. This might allow selective delivery of drugs into specific cells. 

Other uses might be as part of environmental chemical detectors, or in signalling or computational systems. All such possibilities remain to be demonstrated, but they indicate the wide range of applications that chemists envisage for the components they are creating.

The next steps will include developing other feasible components, and combining them into molecular assemblies with useful applications.

1. Wang, Y., Sun, J., Liu, Z. Nassar, M. S., Botros, Y.Y. & Stoddart, J. F. Radically promoted formation of a molecular lasso. Chemical Science 8, 2562-2568 (2017). | article